Q & A: Bilateral Thyroid Nodules in a Cat, But Normal T4 and Free T4?

Agatha is an 11-year-old F/S DSH first seen 3 months ago. The owners complained that she had beeen moping around for the past week and was more "clingy" than normal. She had vomited twice and urinated outside of the box on a few ocassions.  My physical examination at that time was completely normal. Her heart rate was 168 bpm, there were no palpable thyroid nodules, and her weight was 11.3 pounds.

I saw the cat again last week, with the  new complaint of sounding hoarse for 3 weeks. The cat was also eating and drinking less, and she was lethargy and less active. My physical examination revealed that  her body weight was down to 10.2 pounds (i.e., a 1 pound weight loss). The cat also had mild anisocoria, and now I could palpate bilateral thyroid nodules!

I performed routine blood work (CBC, serum chemistry panel) which was completely normal. Her serum T4 value was also normal at 1.5 μg/dl (reference range, 0.8 - 4.0 μg/dl), and the free T4 by dialysis was normal at 23 nmol/L (reference range, 10-50 nmol/L).

It's amazing how much this cat has deteriorated in just 3 months.  How can you explain the cat's thyroid goiter with the normal T4 and free T4 results? Do my results rule out thyroid disease? 

My Response:

Both the serum thyroid tests and history rule out hyperthyroidism, but this cat could still have thyroid hyperplasia or neoplasia. The cervical masses you palpate certainly may be thyroid nodules but could also be lymph nodes, parathyroid tumors, or another type of subcutaneous tumor.

I'd start with fine needle aspiration of the cervical masses. Those results will dictate where our workup should go next. If those results are consistent with thyroid tissue, the next step would be to do thyroid scan (scintigraphy) in order to document that the cervical tumors are indeed thyroid in origin and to rule out thyroid carcinoma.

Q & A: How is the Urinary Cortisol Creatinine Ratio Calculated?

This patient is a 5.5-year-old male neutered Westie that presents with the main complaints of polyuria and polydipsia (PU/PD). The results of a CBC and serum chemistry panal were normal. Strangely, however, the dog has glucosuria with no hyperglycemia. We have run multiple samples on different days of both blood and urine, all showing positive glucosuria but normoglycemia.

I submitted a urine cortisol:creatinine ratio (UCCR)to screen for Cushing's syndrome. It was not the ideal, home-caught, first in AM urine sample. It was free catch urine sample collected here at the clinic. Results show a UCCR ratio of 115. But the urine cortisol is 8.5 μg/dl (normal for Idexx laboratories reference range) and the creatinine is 23.1 mg/dl (low for the reference range). So, am I correct to interpret that the ratio is high because the creatinine is low and not because the cortisol is high? Can Cushing's syndrome be ruled out, or should I proceed to further Cushing's diagnostics?

My Response:

We do the UCC-ratio to correct for increased/decreased filtration and we therefore ought to look at the ratio, not the individual results. Therefore we cannot rule out Cushing's syndrome based on this result. You could, however, repeat measurements on a few home collected, morning samples. It is interesting that the serum alkaline phosphatase is normal in this, which, although still possible, makes hyperdrenocorticism less likely. It still is an important differential though. You could also run a fructosamine to check for chronic relative hyperglycemia.

Q & A: How Does Human Addison's Compare to the Canine Disease?

I don't know if I should even ask this but a situation in my family has me curious. My sister-in-law was diagnosed with pituitary-dependant Addison's disease over five years ago. She has been treated since that time with florinef and prednisone and has been doing well. Recently she had a recheck and an ACTH stimulation test while on treatment and she had a resting cortisol around 10 µg/dl and post around 20 µg/dl. 

Now she's being weaned off of treatment and told her pituitary and adrenals are fine. I've never done an ACTH stimulation test on an animal I'm treating for Addison's disease after it's diagnosed and was wondering about the rational for doing that. Is human Addison's disease curable? Is there something completely different in human Addison's from the canine disease, or am I just missing something? 

If anyone has an opinion and would like to share I'd appreciate it. Curiosity is getting the best of me. 
Thank you.

My Response:

It sounds to me as if they didn't believe the diagnosis of Addison's disease so they repeated the ACTH stimulation test. Addison's disease doesn't resolve once it develops (in either dogs or humans), and there is no such thing as "pituitary-dependent" Addison's disease.

On a brighter note, its's great news that your sister-in-law is normal!

Couldn't you theoretically get glucocorticoid deficiency from lack of production of ACTH? (Kind of like a central diabetes insipidus dog having a central lesion?)

My Response:

Absolutely. But pituitary ACTH deficiency is "secondary" hypoadrenocorticism, not Addison's disease.

Sorry to be such a stickler about terminology, but when Sir Thomas Addison described the disease that now uses his name, all of the patients had "primary" hypoadrenocorticism with complete destruction of both adrenal cortices.Therefore, the term Addison disease should be restricted to those patients with the primary form of the disorder (ie, those that have both glucocorticoid and mineralocorticoid deficiency).

There is no such disease as pituitary Addison's disease. Why? Because, like we all know, pituitary ACTH deficiency can not cause destruction of the adrenal gland or lead to mineralocorticoid deficiency. ACTH deficiency would only cause cortisol deficiency.

When we use the term Addison's so loosely, it becomes very confusing. It really would be best to avoid the use of the term completely. But we know that will never happen!

Q & A: Is a High Free T4 Alone Diagnostic for Hyperthyroidism?

I have a 12 year old male neutered Maine coon cat that has a free T4 (measured by equilibrium dialysis) of 57.9 nmol/L (normal is up to 50 nmol/L). The cat has stable weight and no real signs of hyperthyroidism. Other blood is good. Just wondering how we should follow up. I am contemplating re-assessing in a month or two? What is the correct approach to this case? 
Thanks in advance.

My Response:

Monitor the cat's body weight, heart rate, thyroid size, and serum total T4 concentrations every 2-3 months.

Hyperthyroidism is a clinical diagnosis. The finding of a high serum free T4 value means nothing unless you have clinical signs, or a palpable thyroid nodule, or both.

How Do We Make Desmopressin Dose Adjustments in Dogs or Cats with Diabetes Insipidus?

Once a diagnosis of diabetes insipidus has been confirmed, the next step to start replacement treatment with desmopressin.

Initial treatment with desmopressin

Recommended initial doses of desmopressin vary depending on the route it is being administered. In most cats and smaller dogs, 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia (see Table below).  Larger dogs may require up to 4 to 5 drops twice daily. Use of a tuberculin or insulin syringe allows for more accurate dosing. Application of desmopressin into the conjunctival sac may cause local irritation, as the solution is acidic. Some animals may object to the daily eye drops, making this route of administration ineffective.

With the subcutaneous route of administration, the initial recommended dose is 1.0 to 5.0 μg once or twice daily, depending on the size of the animals. If the nasal solution (100 µg /ml) were used for this purpose, one would inject only 0.01 to 0.05 ml (or 1 to 5 U with a U-100 insulin syringe). With the oral tablets, a starting dose of 0.05 mg to 0.2 mg (50 to 100 µg) once or twice daily is initiated.

Desmopressin dose adjustments

In dogs and cats with central diabetes insipidus, daily administration of desmopressin may completely eliminate polyuria and polydipsia. However, because of individual differences in absorption and metabolism, the dose required to achieve complete, around-the-clock control varies from patient to patient. The maximal effect of desmopressin occurs from 2 to 8 hours after administration, and the duration of action varies form 8 to 24 hours. Larger doses of the drug appear to both increase its antidiuretic effects and prolong its duration of action; however, expense can become a limiting factor for some owners.

No matter what route of administration is used, the daily dose should be gradually adjusted as needed to control signs of polydipsia and polyuria. The morning and evening doses can be adjusted separately if needed.

Adverse effects of desmopressin 

Desmopressin is relatively safe for use in animals with central diabetes insipidus. Adverse effects of desmopressin are uncommon, but overdosage can lead to fluid retention, hyponatremia, and decreased plasma osmolality. Although extremely rare, fluid intoxication associated with desmopressin overdosage can lead to CNS disturbances including depression, increased salivation, vomiting, ataxia, muscle tremors, coma and convulsions. In such instances, furosemide can be given to induce diuresis.

To avoid the potential problem of overdosage, it is recommended that animals not be allowed free access to water immediately after each dose of desmopressin, especially if severe polydipsia and polyuria have redeveloped. Without such short-term (1 to 2 hours) water restriction, the cat many consume excessive amounts of water that cannot be subsequently excreted, as the desmopressin is absorbed and has its peak antidiuretic effects on the renal tubules.

Cost of desmopressin

The principle drawback with the use of any of the desmopressin preparations in the treatment of central diabetes insipidus is the drug’s considerable expense.  The oral route of administration is the most expensive, while the subcutaneous route of administration (using the sterilized nasal solutions) is generally the most cost-effective.

Click on Table to enlarge.

What Drugs Do We Use to Treat Diabetes Insipidus?

Treatment with arginine vasopressin (antidiuretic hormone of humans, dogs, and cats) or its analogues restores medullary hypertonicity and a normal urinary concentrating ability in animals with central diabetes insipidus. Historically, ADH tannate in oil, an extract of arginine vasopressin prepared from bovine and porcine pituitary glands, was administered every 2 to 3 days as needed to control polyuria and polydipsia. Because this product is no longer available, desmopressin acetate, a synthetic analogue of arginine vasopressin with prolonged and enhanced antidiuretic activity, has become the drug of choice for the treatment of central diabetes insipidus in dogs and cats.

DESMOPRESSIN PREPARATIONS
Desmopressin acetate is available in preparations for intranasal, parenteral (injectable), or oral administration (see Table below).

Nasal sprays or solutions of desmopressin

The nasal formulations are supplied with 2 different delivery systems: either a spray pump or a rhinal tube delivery system (see Table below), in which the desmopressin is “sprayed” or “blown” into the nose, respectively. Obviously, most dogs or cats will not tolerate either of these intranasal delivery methods.  Drops placed in the conjunctival sac provide a more suitable alternative for animals.

With the rhinal tube delivery formulation (DDAVP Rhinal Tube®, Sanofi Aventis), the desmopressin is packaged with a small, calibrated plastic catheter so that exact amounts of the drug can be measured and administered.  The calibrated rhinal tube has four graduation marks that measure amounts of 0.05 ml, 0.1 ml, 0.1 ml, and 0.2 ml and thereby can deliver doses of 5 to 20 µg of desmopressin).  Although this system allows for accurate dosing, it is awkward to use. In addition, because this rhinal tube delivery system is not available as a generic product, this formulation is quite expensive.

The most common intranasal formulations of desmopressin are marketed as nasal sprays or solutions equipped with compression pump that delivers 10 µg of drug with each spray. For use in dogs and cats, this spray bottle should be opened (a plier may be neccessary to break the seal) and the desmopressin solution transferred to a sterile vial; this dispensing vial then allows one to place the desmopressin drops within the animal’s conjunctival sac.

These intranasal preparations of desmopressin are generally supplied as a concentration of 100 µg/ml; depending on the size of the drop, one drop of nasal solution corresponds to 1.5 to 4 µg of desmopressin. One highly concentrated nasal solution (1.5 mg/ml) is marketed for use in hemophilia (see Table below), but it should not be used to treat animals with diabetes insipidus because of the strong likelihood of overdosage.

In most cats and smaller dogs, 1 to 2 drops of the intranasal preparation administered once or twice daily are sufficient to control polyuria and polydipsia.  Larger dogs may require up to 4 to 5 drops twice daily. Use of a tuberculin or insulin syringe allows for more accurate dosing. Application of desmopressin into the conjunctival sac may cause local irritation, as the solution is acidic. Some animals may object to the daily eye drops, making this route of administration ineffective.

Oral desmopressin tablets

The oral preparation of desmopressin is available both as a sublingual dissolve melt tablet (not suitable for treating cats) and as 0.1 mg and 0.2 mg tablets. Each 0.1 mg (100 µg) tablet is roughly comparable to 5-10 µg (1-2 large drops) of the nasal solution (see Table below).

The tablet form of desmopressin is a more cost-prohibitive alternative compared with the conjunctival or subcutaneous routes of administration. The cost of daily oral desmopressin in animals is roughly 2.5-times that of the cost of conjunctival drops, and roughly 6 times the cost of subcutaneous injections of desmopressin. For some pet owners, however, the use of a tablet form may prove to be a more convenient, or the only possible route of administration that is possible.

Injectable desmopressin solutions for SC or IV use

An injectable sterile solution of desmopressin acetate (4 µg/ml) marketed for intravenous use is available (see Table) and can be used in animals with diabetes insipidus. However, the cost of the injectable desmopressin is approximately 7 to 15 times higher per µg than the intranasal preparation, making this formulation cost-prohibitive for use in most dogs and cats.

To circumvent this cost issue, the intranasal form of desmopressin – although not designed for parenteral use – can be given subcutaneously to cats with excellent results.

Because the nasal forms of desmopressin are not considered to be sterile, however, it is best to first sterilize the product by passing the nasal solution through a 0.2 micron bacteriostatic syringe filter. Clinically the nasal and injectable preparations of desmopressin induce indistinguishable responses when administered subcutaneously.

To make dosing easier, the desmopressin is best administered with an U-100 low-dose insulin syringe. The solution can be diluted in sterile physiologic saline to make dosing easier.

The subcutaneous route of desmopressin administration has many advantages over the other routes of administration. These advantages include the following:

• First, drug appears to be most effective when administered via the subcutaneous route.
  
• Second, the duration of action is longer after subcutaneous injection than when administered orally or via the conjunctival sac.
  
• Third, because of the smaller subcutaneous doses required to control signs (about 15% and 40% of the oral and conjunctival doses, respectively), the cost of treatment is greatly reduced.
  
• Fourth, many cats seem to prefer long-term subcutaneous injections to the chronic use of eye drops or oral medication.

Company Web sites for more information:
Sanofi Aventis
Ferring Pharmaceuticals
CSL Behring
Bausch and Lomb
Hospira
Teva Pharmaceuticals
Apotex Corporation

Desmopressin acetate is also available generically (many companies) and may also be known by the following synonyms and internationally registered trade names:
Concentraid®, D-Void®, Defirin®, Desmogalen®, Desmospray®, Desmotabs®, Emosint®, Minurin®, Nocutil®, Octim®, Octostim®, or Presinex®

Diagnosis of Diabetes Insipidus: Is the Water Deprivation Test Necessary?

Several different diagnostic approaches can be used to confirm and distinguish central diabetes insipidus, nephrogenic diabetes insipidus and primary (psychogenic) polydipsia. The water deprivation test is generally considered by most authorities to be the best diagnostic test to differentiate between these disorders. However, the water deprivation test has many disadvantages, which include the following:

• The test is very labor intensive
  
• The test can be difficult to perform correctly
  
• The test is quite unpleasant for the dog or cat
  
• The test relies heavily on repeated emptying of the bladder
  
• The test can lead to untoward complications
  
• The test can lead to misdiagnosis in some animals

A simpler and more practical method of diagnosis that I recommended as an alternative to water deprivation testing is evaluation of the clinical response to a closely monitored therapeutic trial with the vasopressin analogue, desmopressin (DDAVP).

Use of the therapeutic trial with desmopressin as a diagnostic test 

This approach is less complicated and time consuming than the water deprivation test, and is certainly easier on the cat. The cost of the two approaches varies according to circumstances but is often comparable. Again, before a desmopressin trial is initiated, it is extremely important to rule out all other common causes of polyuria and polydipsia, limiting the differential diagnosis to central diabetes insipidus, primary nephrogenic diabetes insipidus, and primary (psychogenic) polydipsia. For further information, see my previous blog posts.

To perform the test, the owner should first measure the animal's 24-hour water intake for 2 to 3 days before desmopressin is initiated, allowing free-choice water intake. The dog or cat is then treated with therapeutic dosages of desmopressin (see our next post, What Drugs Do We Use to Treat Diabetes Insipidus).

For the purposes of this test, the desmopressin ideally is administered subcutaneously at the dosage of 1.0 to 4.0 μg twice daily for a period of 5 to 7 days. If subcutaneous injections cannot be given, administration of desmopressin by the conjunctival (1-5 drops twice daily) or oral routes (0.05-2.0 mg twice daily) can be used instead. During this treatment period, the owner should continue to measure the animal’s daily water intake and monitor the degree of urine output.

A dramatic reduction in water intake (>50% of pre-treatment measurements) and polyuria strongly suggests a diagnosis of central diabetes insipidus, whereas a lack of any reduction in polydipsia and polyuria is most consistent with primary nephrogenic diabetes insipidus. With more prolonged treatment, water consumption and urine output should completely normalize in dogs and cats with central diabetes insipidus.

In any older dog or cat that develops diabetes insipidus, one should consider pituitary imaging with computerized tomography or magnetic resonance imaging to exclude a pituitary mass. This is especially true if the affected animal has associated neurological signs.




Computerized tomography (CT) image of the brain of a cat with diabetes insipidus. Note the very large pituitary tumor invading the hypothalamus.

Diagnostic Approach to PU/PD: Urine Specific Gravity

Urinalysis is a major key in determining the presence of a water balance problem and the disorder causing the polyuria and polydipsia. The most important features of urinalysis are: the SG or osmolality; the presence or absence of glucose, protein or bacteria; and the cellularity of the sample.

A urine SG less than 1.030 in dogs and 1.035 in cats suggests a concentrating defect and supports the complaint of polyuria. Persistent glycosuria is diagnostic for primary renal glycosuria or, more commonly, diabetes mellitus. Significant proteinuria in the presence of an inactive urinary sediment and dilute urine can be associated with hyperadrenocorticism, pyelonephritis, pyometra, glomerulonephritis or other glomerulopathy.

An active urine sediment (pyuria, hematuria or bacteriuria) in a sample obtained by catheterization or cystocentesis supports urinary tract infection and possible pyelonephritis. Because urine sediment examination may be misleading in an extremely dilute urine sample, a urine culture should always be done to rule out pyelonephritis, regardless of sediment examination findings.

If the results of the above tests are unhelpful the direction of further diagnostic work-up can often be based on the urine SG (see Table below). For example, dogs and cats with a SG greater than 1.030--1.035 without glycosuria, are probably not polyuric and need no further work-up, at least for polyuria and polydipsia.

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Differential diagnosis based on urine specific gravity (SG) determination in animals with normal results of initial tests (CBC, serum biochemical profile and urinalysis).

Urine SG of 1.001--1.007

• Atypical hyperadrenocorticism (most common; always rule out first!)
  
• Atypical leptospirosis
  
• Psychogenic polydipsia
  
• Diabetes insipidus (complete)

Urine SG of 1.008--1.029

• Atypical hyperadrenocorticism (most common!)
  
• Atypical leptospirosis
  
• Early renal disease
  
• Typical and occult pyelonephritis
  
• Hyperthyroidism (cats)
  
• Psychogenic polydipsia
  
• Diabetes insipidus (partial)

Urine SG greater than 1.030 (without glycosuria)

• probably No further work-up for polyuria and polydipsia needed.

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Urine SG less than 1.008 A urine SG consistently less than 1.008 in a middle-aged to older dog is usually associated with diabetes insipidus, psychogenic polydipsia, atypical hyperadrenocorticism or atypical leptospirosis.

In these dogs with atypical hyperadrenocorticism, polyuria and polydipsia are major clinical signs but other characteristic clinical signs are mild or absent. In addition, these dogs with atypical disease may lack the serum biochemistry abnormalities commonly associated with hyperadrenocorticism (i.e. elevated serum alkaline phosphatase activity and hypercholesterolaemia). Results of adrenal function tests in these dogs are usually consistent with mild hyperadrenocorticism.

More recently an atypical form of leptospirosis has been recognized. These dogs present with an acute onset polyuria and polydipsia, hyposthenuria or isosthenuria, but no other laboratory abnormalities. Diagnosis of leptospira infection can be confirmed by positive leptospirosis serology or use of molecular detection of leptospiral DNA by polymerase chain reaction (PCR) testing performed on urine samples.

In general, when considering polyuric dogs with a urine SG less than 1.008, hyperadrenocorticism and atypical leptospirosis should be ruled out first before testing for central diabetes insipidus and primary polydipsia. There are several reasons for making this recommendation: the latter two disorders of water metabolism are much less common than hyperadrenocorticism (see Table below); the diagnostic tests of choice to differentiate these disorders – the water deprivation test or a therapeutic trial with the AVP-analogue desmopressin – are time-consuming and expensive. Also, dogs with hyperadrenocorticism may respond to these tests in a manner similar to dogs with central diabetes insipidus, resulting in a misdiagnosis. Moreover, water deprivation testing a dog with leptospirosis would be a major contraindication because of the possibility of causing significant patient morbidity.

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Differential rule outs for polyuria and polydipsia in dogs and cats, listed from most to least common. Dogs

• Hyperadrenocorticism
  
• Diabetes mellitus
  
• Chronic renal failure
  
• Pyelonephritis
  
• Pyometra
  
• Hypercalcaemia
  
• Atypical leptospirosis
  
• Psychogenic polydipsia
  
• Diabetes insipidus
  
• Liver disease
  
• Hypoadrenocorticism
  
• Acromegaly
  

Cats

• Chronic renal failure
  
• Diabetes mellitus
  
• Hyperthyroidism
  
• Hypercalcaemia
  
• Pyelonephritis
  
• Hypokalaemia
  
• Acromegaly
  
• Postobstructive diuresis
  
• Hyperadrenocorticism
  
• Hypoadrenocorticism
  
• Diabetes insipidus

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In cats, a urine SG consistently less than 1.008 is associated with either diabetes insipidus or hyperthyroidism. Obviously, hyperthyroidism should be ruled out first before initiating testing procedures for diabetes insipidus. It is also important to realize that the finding of a urine SG less than 1.008 in a cat or dog excludes mild (occult) renal disease, so precautions associated with the water deprivation test are not necessary.

Urine SG between 1.008 and 1.029

A urine SG of 1.008--1.012 or greater (but less than 1.030) can be associated with hyperadrenocorticism (dogs), hyperthyroidism (cats), or stage 1 renal insufficiency (including atypical leptospirosis) or pyelonephritis, as well as psychogenic polydipsia and partial forms of diabetes insipidus. 

Again, when considering animals with a urine SG greater than 1.008 hyperadrenocorticism and hyperthyroidism should first be ruled out. With this group of disorders, pyelonephritis and early renal insufficiency should next be ruled out before evaluating the animal for psychogenic polydipsia and diabetes insipidus with a water deprivation test. Performing a water deprivation test as a diagnostic tool in the face of unsuspected renal insufficiency or pyelonephritis could induce overt renal failure or urosepsis. To avoid this complication, a sensible approach is to do the following:

1. Perform a urine culture to help exclude pyelonephritis and associated urinary tract infection.
   
2. Consider leptospirosis serology and urine PCR testing.
   
3. Evaluate renal size and architecture by abdominal radiography or, preferably, renal ultrasonography. The ultrasonographic appearance of renal parenchymal disease (chronic renal failure) includes increased cortical echogenicity and loss of a distinct corticomedullary junction. The kidneys may appear smaller than normal and have an ill-defined or irregular border. Similar sonographic findings, in addition to a dilated renal pelvis, are characteristic of pyelonephritis.

If urine culture results are negative, leptopirosis serology and urine PCR testing are negative, and radiographic or ultrasonographic findings are equivocal, a creatinine or iohexol clearance test or renal biopsy may be indicated. In rare cases, the urine culture may be negative even if pyelonephritis is present. If clinical or ultrasonographic findings suggest occult pyelonephritis, a therapeutic trial with an appropriate antibiotic (e.g. enrofloxacin) should be instituted.

In the next post, I will talk about when water deprivation testing is needed in the workup of dogs and cats with PU/PD.

Diagnostic Approach to Polyuria and Polydipsia

Differentiating between the causes of polyuria and polydipsia (PU/PD) is relatively easy when the different disorders are manifested in their classic forms. For example, polyuria that develops after a known head trauma, continues after water restriction and decreases after AVP administration does not require additional tests to justify the diagnosis of central diabetes insipidus. A diagnosis of congenital nephrogenic diabetes insipidus is equally clear if polyuria occurs in a young animal with similarly affected litter mates that have normal screening laboratory tests (including renal function), negative urine cultures and whose polyuria fails to respond to fluid restriction or administration of AVP analogues (e.g. desmopressin).

Often, however, the clinical setting is of minimal help in making a diagnosis and it is then necessary to perform more detailed diagnostic tests. The initial information gathered should allow the inclusion or exclusion of the many common medical disorders associated with polyuria and polydipsia before a diagnostic work-up for the less common disorders of central diabetes insipidus, primary nephrogenic diabetes insipidus or psychogenic polydipsia is embarked upon.

Measurement of water consumption
The first step in any suspected case of polyuria and polydipsia is to establish that the problem actually exists, preferably by a combination of history, random urine SG determinations and, if necessary, home measurement of water consumption over several days.

If the daily water intake is found to be normal or if a random urine SG determination is >1.035, additional history should be obtained to rule out other urinary tract disorders (such as urinary incontinence or dysuria) that commonly are confused with polyuria. If, however, random urine SG are consistently <1.030 in dogs and <1.035 in cats, and daily water intake is >100 ml/kg for dogs and 45 ml/kg for cats, polyuria and polydipsia are indeed present and a diagnostic work-up to determine the cause is warranted.

Minimum clinicopathological data
Once a problem of water balance is confirmed, a practical diagnostic approach is to first rule out the more common causes of polyuria and polydipsia in dogs and cats. Recommended initial diagnostic tests include:

• Complete blood cell count (CBC)
  
• Serum biochemical profile with electrolytes
  
• Serum total thyroxine (T4) determination in middle-aged to older cats

A careful evaluation of this initial database, together with the history and results of physical examination, usually provides the diagnosis immediately (e.g. overt renal failure, hyperthyroidism or diabetes mellitus) or offers clues to as to the underlying cause of the polyuria and polydipsia (see Table below). For example, dogs with hyperadrenocorticism commonly have a stress leucogram (i.e. neutrophilia, lymphopenia and eosinopenia). Over 90% of dogs with hyperadrenocorticism also have high alkaline phosphatase (ALP) activity, whereas over half have hypercholesterolaemia.

In contrast, physical examination findings and routine blood work are generally unremarkable in animals with less common causes of polyuria and polydipsia such as central diabetes insipidus, primary nephrogenic diabetes insipidus and psychogenic polydipsia. When abnormalities are present, they are usually secondary to dehydration caused by water restriction by the owner. Such abnormalities may include a slightly increased packed cell volume (PCV) or hypernatraemia.

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Initial work-up for polyuria and polydipsia in dogs and cats.

Signalment and history

• Age, breed and sex
  
• Reproductive history (intact female?)
  
• Changes in diet or environment?
  
• Overall general health (weight loss or gain, lethargy, vomiting or diarrhoea?)
  
• Appetite normal, increased or decreased?
  
• Drug administration (glucocorticoids, anticonvulsants, diuretics?)

Physical examination

• Kidneys small or misshapen? (chronic renal disease)
  
• Kidneys large? (pyelonephritis, lymphosarcoma)
  
• Hepatomegaly? (hyperadrenocorticism, diabetes mellitus)
  
• Peripheral lymphadenopathy? (lymphosarcoma with hypercalcaemia)
  
• Perianal mass? (anal sac adenocarcinoma with hypercalcaemia)
  
• Vaginal discharge? (pyometra)
  
• Alopecia? Pot belly? (hyperadrenocorticism)
  
• Thyroid mass? (hyperthyroidism)

Complete blood count (CBC), serum biochemical profile and electrolytes, serum thyroxine

• High urea or creatinine? (renal failure)
  
• Hyperglycaemia? (diabetes mellitus)
  
• High alkaline phosphatase activity (hyperadrenocorticism)
  
• Hypercholesterolaemia? (hyperadrenocorticism)
  
• Hypercalcaemia?
  
• Hypokalaemia?
  
• High thyroxine? (hyperthyroidism)

Complete urinalysis and urine culture

• Low urine specific gravity (confirms and defines polyuria)
  
• Proteinuria? (hyperadrenocorticism, pyometra, pyelonephritis, glomerulonephritis)
  
• Glucosuria +/- ketonuria? (Diabetes mellitus)
  
• Active urine sediment? (infection, pyelonephritis)
  
• Positive bacterial culture? (infection, pyelonephritis)

Abdominal radiography or ultrasonography

• Small kidneys with ill-defined renal or irregular border (renal failure)
  
• Increased cortical echogenicity, indistinct corticomedullary junction (renal failure)
  
• Dilated renal pelvis (pyelonephritis)

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Our next blog post we will continue discussing the diagnostic approach to PU/PD, concentrating on the urine's specific gravity.

What's the Differential Diagnosis of Polydipsia and Polyuria in Dogs and Cats?

There are many potential causes of polyuria and polydipsia.  Primary disorders of water balance (i.e. central diabetes insipidus, primary nephrogenic diabetes insipidus and primary polydipsia) although uncommon, should always be considered in the differential diagnosis of polyuria and polydipsia. In general, animals with these disorders have only one laboratory abnormality; a low urine specific gravity (SG) or osmolality.

In most instances the more common causes of polyuria and polydipsia (e.g. hyperadrenocorticism, chronic renal failure, pyelonephritis and pyometra) have other specific and obvious abnormalities on screening laboratory tests (complete blood cell count, serum biochemical profile and urinalysis). In some cases, however, a low urine SG is the only abnormality found in animals with these latter disorders.

The work-up for polyuria and polydipsia can be tedious, time-consuming, expensive, confusing and not without significant patient morbidity, especially in those dogs and cats with normal or near-normal screening test results. This chapter focuses on the diagnostic approach, especially the problems associated with testing, and the treatment of dogs and cats with disorders of water balance.

Differential diagnosis
The causes of polyuria and polydipsia can be divided into those that cause primary polydipsia (with secondary polyuria) and those that cause primary polyuria (with compensatory polydipsia). These are listed in the table below.

The major cause of primary polydipsia in dogs is psychogenic polydipsia. In contrast, the causes of primary polyuria are much more numerous and can be subdivided into the categories of: central diabetes insipidus; primary nephrogenic diabetes insipidus; secondary nephrogenic diabetes insipidus; and osmotic diuresis.

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DIFFERENTIAL DIAGNOSIS OF POLYDIPSIA AND POLYURIA

1. Primary polydipsia

• Psychogenic polydipsia (compulsive water drinking)
  
• Dipsogenic diabetes insipidus (thirst centre abnormality)
  
• Metabolic disorders (e.g. hyperthyroidism, hepatic failure)

2. Primary polyuria

Central diabetes insipidus (neurogenic, cranial, ADH-responsive)

• Idiopathic
  
• Trauma-induced
  
• Neoplastic
  
• Post-hypophysectomy

Primary nephrogenic diabetes insipidus (congenital or familial)

Secondary nephrogenic diabetes insipidus (acquired)

• Acromegaly
  
• Chronic renal disease
  
• Drug administration
  
• Liver disease
  
• Hyperadrenocorticism
  
• Hypercalcaemia
  
• Hyperthyroidism
  
• Hypoadrenocorticism
  
• Hypokalaemia
  
• Leptospirosis
  
• Postobstructive diuresis
  
• Pyelonephritis
  
• Pyometra

Osmotic diuresis (increased renal tubular solute load)

• Diabetes mellitus
  
• Primary renal glycosuria (e.g. Fanconi’s syndrome)
  
• Postobstructive diuresis
  
• Renal failure
  
• Leptospirosis

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In our next blog post, I will talk about my approach to working up the dog or cat with polyuria or polydipsia.